One-carbon metabolism, MTHFR polymorphisms, and risk of breast cancer
One-carbon metabolism, MTHFR polymorphisms, and risk of breast cancer
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DOI：
10.1158/0008-5472.can-04-2630
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发表时间：
2005-02-15
期刊：
影响因子：
11.2
通讯作者：
Santella, RM
中科院分区：
文献类型：
--
作者：
Chen, J;Gammon, MD;Santella, RM
从流行病学研究中积累的证据表明，乳腺癌的风险随着叶酸和相关B族维生素的摄入增加而降低。我们研究了维生素B摄入量以及关键的一碳代谢基因[即亚甲基四氢叶酸还原酶(MTHFR)677C>；T和I1298A>；C]的两个多态对乳腺癌风险的独立和联合影响。这项研究使用了以人群为基础的病例对照研究的资源，其中包括1,481例病例和1,518例对照。在非补充剂使用者中，观察到维生素B摄入量与乳腺癌风险之间存在显著的负相关。与非补充剂使用者(高危个体)相比，非补充剂使用者在饮食叶酸摄入量的最高五分之一[优势比(OR)，0.61；95%可信区间(95%CI)，0.41-0.93]中乳腺癌风险的降低最大。MTHFR 677T变异等位基因与乳腺癌风险增加相关(P，趋势=0.03)，其多因素调整OR值为1.37(95%CI，1.06~1.78)。1298C变异等位基因与乳腺癌风险呈负相关(P，趋势=0.03)，可能是由于该等位基因与低危等位基因677C连锁所致。MTHFR与乳腺癌的关联在不使用复合维生素补充剂的女性中更为突出。与叶酸摄入量高的677CC人群相比，膳食叶酸摄入量最低(OR，1.83；95%CI，1.13~2.96)或总叶酸摄入量(OR，1.71；95%CI，1.08~2.71)的677TT女性患乳腺癌的风险增加最为明显。从公共卫生的角度来看，重要的是确定风险因素，例如维生素B摄入量低，这些因素可能指导有效的疾病预防战略。
Accumulating evidence from epidemiologic studies suggests that risk of breast cancer is reduced in relation to increased consumption of folate and related B vitamins. We investigated independent and joint effects of B vitamin intake as well as two polymorphisms of a key one-carbon metabolizing gene [i.e., methylenetetrahydrofolate reductase (MTHFR) 677C>T and I1298A>C] on breast cancer risk. The study uses the resources of a population-based case-control study, which includes 1,481 cases and 1,518 controls. Significant inverse associations between B vitamin intake and breast cancer risk were observed among non-supplement users. The greatest reduction in breast cancer risk was observed among non-supplement users in the highest quintile of dietary folate intake [odds ratio (OR), 0.61; 95% confidence interval (95% Cl), 0.41-0.93] as compared with non-supplement users in the lowest quintile of dietary folate intake (high-risk individuals). The MTHFR 677T variant allele was associated with increased risk of breast cancer (P, trend = 0.03) with a multivariate-adjusted OR of 1.37 (95% CI, 1.06-1.78) for the 677TT genotype. The 1298C variant allele was inversely associated with breast cancer risk (P, trend = 0.03), and was likely due to the linkage of this allele to the low-risk allele of 677C. The MTHFR-breast cancer associations were more prominent among women who did not use multivitamin supplements. Compared with 677CC individuals with high folate intake, elevation of breast cancer risk was most pronounced among 677TT women who consumed the lowest levels of dietary folate (OR, 1.83; 95% CI, 1.13-2.96) or total folate intake (OR, 1.71; 95% CI, 1.08-2.71). From a public heath perspective, it is important to identify risk factors, such as low B vitamin consumption, that may guide an effective prevention strategy against the disease.